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Many breast cancer patients need to take chemotherapy drugs for a long period of time, such as tamoxifen which is usually prescribed for five years.

To achieve the best results from chemotherapy it’s necessary to correctly balance the level of the drug in the body by changing the dose on later cycles. Patients need sufficiently high enough doses to kill their breast cancer cells but not too high that they are unable to cope with the harsh side-effects.

However, each person will take to chemotherapy differently based on factors such as body size, age, other drugs and foods they are taking and how hard their kidney and liver work hard to flush foreign toxins. Current standard practice for measuring the correct dose doesn’t take all these factors into account, resulting in imprecise dosing for individual patients. Some may receive doses of chemo that are too toxic for their body, and some may receive too little to be effective.

A blood test can help determine the right dose; however going into the clinic for a blood test can be cumbersome and inconvenient for women with breast cancer. On a national scale drawing blood samples and transporting them around Australia to labs for analysis is logistically unfeasible for the health system.

Professor Jennifer Martin

Professor Jennifer Martin

NBCF is funding Professor Jennifer Martin’s project which aims to develop a new way of measuring the right dose for each person, which is similar to the finger prick blood test diabetics take several times a day to check their glucose levels.

This finger-prick blood sampling method could be done by health professionals who administer chemo at clinical facilities right across Australia, including remote and regional areas. The test would provide instant information on chemotherapy levels in the blood to assist in accurately tailoring the dose for each individual.

For patients already being treated, the test would also help determine if their dosage needs tweaking to get the best effect from the treatment while minimising side effects.

Achieving appropriate doses of chemotherapy in patients with breast cancer will contribute to improved management of breast cancer care, leading to better survival and better quality of life.

Improved early detection is a critical step in improved outcomes from breast cancer and BreastScreen Australia runs a breast screening program which is proven to reduce deaths from breast cancer.

The screening program schedules all eligible women for a mammogram every two years. However, not every woman has the same level of risk of breast cancer. Some women have a very low risk and some women have a higher risk so this fixed schedule may not detect any tumours early enough.

As our understanding of the risk factors for breast cancer increase – such as family genetics, breast density, obesity and other lifestyle factors such as alcohol – more powerful information could be incorporated into the screening process to provide a better understanding of a woman’s likelihood of developing breast cancer.

Dr Jocelyn Lippey

Dr Jocelyn Lippey

Cancer Australia is working on an improved breast screening program that includes these risk factors. This program will first require a trial of Australian women requiring breast screening to determine its suitability for nationwide adoption.

The success of the trial relies on women participating. The challenge is that with more information being collected and analysed by the new screening program, there may be significant changes to what women usually expect from their routine mammogram.

For example, as a result of her reviewing her risk of developing breast cancer, a woman’s routine screenings may be recommended to be more frequent if she is determined to be at high risk, or less frequent if she is low risk.

This type of divergence from current screening practice may be unsettling for women involved. How such a change in relation to their level of risk is communicated to women by healthcare providers is crucial to ensuring participation in the trial.

Women considering participating will need to fully understand any change to their schedule and feel confident that they are still receiving best-practice screening for breast cancer.

NBCF supports this initiative and has funded Dr Jocelyn Lippey to consult with women and healthcare providers on the most effective way to encourage women to participate in the trial.

Her study will ensure both women and their healthcare providers have the communication tools to understand what the tailored screening trial and subsequent nationwide program will involve, how it will run and what it can achieve, to give the trial and the subsequent program the best chance of being successfully implemented.

The spread of breast cancer, a process called metastasis, is the cause of death in nearly all patients who die of breast cancer.

Around a third of those diagnosed with breast cancer will later develop metastatic breast cancer, but as yet there is no way to know which patients will or when it might occur.

breast cancer researchMetastasis may happen up to 20 years after treatment for the original tumour, causing ongoing fear and anxiety for patients and their families about when or if the disease might come back.
Cancer cells can spread from the primary tumour and lodge in other tissues in the body, such as the bone marrow, and remain alive but not increase in number for many years – a process called metastatic dormancy.

Researchers have not yet discovered how a cell can stay alive but not divide and grow, and why it suddenly starts growing into a detectable secondary cancer.

The aim of this NBCF-funded project is to explore the role of a gene called c-Myc that can potentially control the dormancy of tumour cells and develop ways of  turning this gene on and off and test the ability of a cancer cell to stay dormant.

Professor Robin Anderson and her team are looking to see if dormant tumour cells use c-Myc to preserve their survival until conditions in the body are ideal to support rapid growth into a secondary tumour.

Until now, research into metastatic dormancy has been hampered by the lack of good ways in which to study the process, so Professor Anderson’s study has the potential for a breakthrough in understanding about how cancer returns and ultimately how to stop it.

Women with breast cancer often have additional physical and psychological stresses to cope with during their treatment, many of which are preventable. For example, two thirds of those who are hospitalised with advanced metastatic breast cancer will have a delirium episode at some point during a stay in hospital.

Delirium is a serious medical condition affecting the brain, which results in confused thinking and reduced awareness of environment. It also impacts the ability to communicate at a critical time when being mentally aware and interacting with loved ones is crucial for quality of life.

Women with advanced metastatic breast cancer are at higher risk of delirium due to medical problems such as changes in blood levels of calcium or oxygen, infections, and the side effects of their medications. Each year it is estimated that at least 2000 women with advanced breast cancer experienced delirium before their death during a hospital stay. Delirium is reversible in only half of cases and there is no medication to effectively treat its symptoms.

Delirium is one of the most significant medical complications for those in the final stages of breast cancer. It has serious adverse consequences: it is highly distressing to experience for the person themselves and to witness as a family member, it increases the risk of complication in hospital such as falls, reduced independence and function and cognitive capacity, and is associated with longer hospital stays, higher health care costs and a high mortality rate.

The good news is that delirium is preventable in many cases and recent research has shown that incidences of delirium in older hospitalised adults can be reduced by up to 50 per cent. Additional data is needed specifically for the women with advanced metastatic breast cancer which takes into account other factors such as fatigue and/or limited mobility.

Professor Meera Agar work on breast cancer support

Professor Meera Agar

NBCF-funded Professor Meera Agar and her team will run a trial to collect data on the benefits of methods to avoid delirium episodes. These methods include ensuring they get enough sleep, enhancing physical function, maximising hydration and nutrition and making sure patients are not isolated from sounds and senses which help to keep them grounded.

Professor Agar’s research program aims to reduce the incidence of delirium in women with advanced metastatic breast cancer by 50 per cent, a change which would mean a significant improvement to their quality and length of life.

Research has improved the success rate of breast cancer to 90 per cent, but for women with metastatic breast cancer (when the cancer has spread beyond the breast) modern treatments are only able to prolong life, not stop the cancer progressing.

Targeted therapies are a new class of medicines that have improved the survival and quality of life of breast cancer patients. Targeted therapies are among the last treatment options for metastatic breast cancer patients in the very advanced stages of the disease, and while some patients experience substantial benefit from these medicines, unfortunately, many others either do not respond or experience severe toxicity.

Dr Ashley HopkinsIn this project, Dr Ashley Hopkins will use advanced mathematical techniques aiming to identify predictors of good and bad outcomes to targeted therapies used
in metastatic breast cancer. Dr Hopkins will analyse data that has been collected across a series of clinical trials on targeted therapies to determine who responded well and why, so these drugs can be more accurately prescribed.

Dr Hopkins intends to share the study results so that clinicians and breast cancer patients can assess the benefit and risks of these treatments – such as the likelihood of a positive outcome weighed up against the drugs toxicity.

This type of information can help guide treatment decisions that may improve response rates and decrease toxicity to specific therapies, provide an indicator of when to use alternate therapies or focus on palliative care, which may also lengthen the survival of cancer sufferers.

If the success rates of targeted therapies can be improved, they could be included as options in standard care within the next 10 years, helping to successfully treat women with metastatic breast cancer.

Olaparib is known to be effective treatment for breast and ovarian cancers in people with inherited mutations. Many more patients do not have a genetic risk but have cancers arising from spontaneous mutations. Our clinical trial aims to find out whether olaparib benefits patients with breast or ovarian cancers with non-inherited mutations or abnormalities.

Altered metabolism is a key feature of cancer, with metabolic pathways reprogramed to meet the energy demands of cancer cell growth. However, little is known about the role of increased lipid metabolism in breast cancer. We now show that ACC1, a key regulator of lipid metabolism, is expressed by breast tumours, and that inhibiting ACC1 impairs breast cancer progression. This proposal will validate and characterise ACC1 as a novel therapeutic target for the treatment of breast cancer.

Determine the effects of exercise alone +/- systemic therapy on tumour response, metabolic effects, tumour transcriptome and circulating biomarkers in ER+ve and ER-ve PDX models. Determine the effects of exercise on immunological and metabolic responses, cytokines, tumour vascular density and circulating biomarkers in immunocompetent (MMTV-PyMT) mouse tumour models. To determine the feasibility of a graded exercise program in patients with early breast cancer during the administration of adjuvant chemotherapy or ET.

Millions of women with a type of breast cancer fuelled by the female hormone estrogen have benefited from treatments such as tamoxifen and femara, which in most cases successfully prevent breast cancer returning later in life.

However, a third of these hormone-driven breast cancers develop resistance to preventative treatments and the cancer becomes metastatic, spreading throughout the body.

Treatment resistance is the highest cause of mortality in breast cancer. It’s vitally important to prevent this metastatic stage of breast cancer but as yet there are no effective tests or personalised therapies that can identify or help these women and men.

Dr Liz Caldon

Dr Liz Caldon

NBCF-funded Dr Liz Caldon believes that the survival and quality of life would improve significantly if it was possible to predict from the first diagnosed cancer whether it is likely that someone’s cancer will recur, and then treat any recurrence with drugs that are specifically toxic to hormone resistant breast cancer.

But first she is focusing on improving our understanding of hormone resistant breast cancer, specifically the molecular changes that occur as the cancer cells develop resistance, including which genes might be involved.

With this knowledge she and her team will design better predictive tests that detect the presence of resistant cancer cells well before they start to grow as a secondary cancer. They will also determine if these cells have any particular qualities that mean they could be specifically targeted and destroyed during therapy.

Ultimately, this research project aims to eliminate the development of resistance to treatment and stop recurrence from ever happening, providing hope for women and men with hormone resistant breast cancer.

Thanks to medical research it’s now widely recognised that harnessing the immune system is a powerful way to target and kill cancer.

Patients with high levels of immune cells within their tumour respond better to both standard therapies (radiotherapy and chemotherapy) and therapies designed to enhance the immune response against cancer (immunotherapy). However, many patients don’t have immune cells in their tumours so these treatments are not very effective, and more research is needed.

One potential strategy for these patients is the use of white blood cells which are genetically engineered to eradicate cancer cells. These cells, called ‘chimeric antigen receptor T cells’ (CAR T cells), are very effective in blood cancers but don’t work well in other cancers including breast cancer.

One reason for this is because cancer produces adenosine, a substance which has a powerful ability to suppress the immune system. It creates an environment designed to switch off immune cells, giving the cancer plenty of opportunity to grow unchecked.

Dr Paul Beavis

Dr Paul Beavis

In a four-year NBCF-funded study, Dr Paul Beavis aims to reprogram the CAR T cells to block the effects of adenosine, so the immune system can recognise, find and destroy any cancer in the body.

The adenosine pathway is most relevant in triple negative breast cancer which is the most aggressive and hardest to treat subtype. Development of a successful immunotherapy would be a significant breakthrough and would have a huge impact on the lives of women diagnosed the disease, and particularly for those with triple negative breast cancer.